Mice with altered brain lipoprotein metabolism display maladaptive responses to environmental challenges that may predispose to weight gain.

backgroundThree-month-old neuron-specific lipoprotein lipase (LPL)-depleted mice (NEXLP(-/-)) mice are preobese and have normal body weight before developing obesity by 4.5 months. This series of experiments investigated responses to novel environment stimuli and acute sleep deprivation in preobese NEXLPL(-/-)) mice to test the hypothesis that neuron-specific LPL deletion alters normal adaptive metabolic responses to environmental challenges.

methodsThree-month-old, age- and weight-matched, male NEXLPL(-/-)) (n=10) and wild-type (WT) (n=10) mice were housed in individual metabolic chambers with a 12-hr dark cycle. Food and water intake, locomotor activity, and calorimetry data were recorded in 12-min intervals. Novel environmental responses were elicited by first-time introduction to chambers at dark onset, followed by acclimation, baseline recording, and 6-hr of sleep deprivation on subsequent experimental days.

resultsNEXLPL(-/-)) mice displayed a 1.5-fold greater increase in activity in response to a novel environment than seen in WT controls (P=0.0308), and a two-fold greater increase in food intake following acute sleep deprivation (P=0.0117). NEXLPL(-/-)) mice averaged a 27% higher metabolic rate than WT mice throughout the experiments (P<0.0001). Body weight, composition, and temperature did not differ between murine groups throughout the experiments. Levels of free fatty acid, insulin, glucose, and triglycerides were similar between groups at the terminus.

conclusionsA deficiency in neuronal LPL signaling disrupts normal responses to novel environmental exposure and acute sleep deprivation, a maladaptive response that may contribute to weight gain in genetically predisposed mice, and perhaps humans.